Intraindividual variability in arsenic methylation in a U.S. population

Area of Science:

• Environmental Health
• Toxicology
• Cancer Epidemiology

Background:

• Reduced methylation capacity of inorganic arsenic is linked to increased cancer risk.
• Previous studies relied on single time-point measurements of urinary arsenic metabolites.
• The long latency of arsenic-induced cancers raises questions about the validity of recent methylation pattern estimations.

Purpose of the Study:

• To assess intraindividual variation in arsenic methylation capacity over one year.
• To evaluate the stability of arsenic methylation patterns in individuals with low to moderate exposure.
• To determine the impact of measurement imprecision and temporal variation on methylation pattern assessment.

Main Methods:

• Analyzed urinary inorganic arsenic, monomethylarsonate, and dimethylarsinate distribution in 81 subjects.
• Collected multiple urine samples from each subject over a 1-year period.
• Conducted duplicate sample analyses to assess laboratory measurement imprecision.

Main Results:

• Intraclass correlation coefficients (ICCs) for arsenic species proportions between samples 258 days apart ranged from 0.45 to 0.49.
• ICCs for duplicate sample analyses of species proportions ranged from 0.63 to 0.76.
• ICCs for duplicate sample analyses of arsenic species concentrations were high (0.87–0.93).

Conclusions:

• Individual arsenic methylation patterns demonstrate moderate stability over time.
• Variability in measurements can arise from laboratory imprecision and intraindividual changes.
• This variability may lead to misclassification of methylation status, potentially biasing cancer risk estimates towards the null.